The use of antimicrobials to inhibit the growth of bacteria, fungi and molds in food compositions for oral ingestion is well known. For example, sodium propionate is routinely added to commerical bread to inhibit mold. In spite of the body of literature on this general topic, workers in the medical/veterinary sciences do not appear to have appreciated the special benefits which are afforded when carboxylate antimicrobials are used in the manner of the present invention. In particular, the incorporation of carboxylate antimicrobials in the polymers of the present type, thereby allowing diffusion of the antimicrobial agent from devices fashioned from said polymers and providing a zone of microbial inhibition on tissue surfaces surrounding said devices, has not been suggested heretofore. This is indeed surprising, in light of the pressing need to avoid microbial contamination and possible sepsis in patients undergoing treatment regimens where there is any likelihood of direct communication between the external environment and normally protected tissues and the body cavities.
This oversight on the part of the medical community may have occurred because medical science is only now coming to grips with the problem of massive sepsis due to newer medical techniques. Equally likely is that the carboxylates have been passed over as ineffective antimicrobials in light of the confused state of recent literature.
The doctoral dissertation of Roger L. Stone, entitled "The Requirements for Metabolizable Energy and Nitrogen for Maintenance in Parenterally Fed Sheep", The Ohio State University, published August, 1975, page 37, discloses the use of propionic acid in intravenous solutions. These solutions were administered via a silicone rubber catheter, but no mention is made of any antimicrobial effect of the acid-plus-catheter combination, nor was the silicone rubber impregnated with the propionic acid.
U.S. Pat. No. 2,729,586, issued Jan. 3, 1956 to S. M. Peck, describes therapeutic compositions comprising water-soluble chlorophyll and at least one salt of a C.sub.3 -C.sub.11 monocarboxylic acid.
U.S. Pat. No. 4,002,775, issued Jan. 11, 1977, to J. J. Kabara, describes fatty acids and derivatives as antimicrobial agents. According to the Kabara patent, neither caproic (hexanoic) nor caprylic (octanoic) acid are inhibitory to any of the microorganisms under the test conditions. Yet, properly used in the manner disclosed herein, these two carboxylate materials have now been found to be particularly potent, yet safe and highly preferred, antimicrobial agents which are capable of prolonged diffusion from polymers, especially silicone elastomers, to provide a zone of microbial inhibition around catheters, and the like.
U.S. Pat. No. 2,154,449, Hoffman, et al., 1939, describes the use of aliphatic carboxylic acids (C.sub.3 -C.sub.12) or their salts as mold inhibitors in foods. The patent teaches the use of these acids to protect materials susceptible to mold, including tobacco, paper, leather, textiles, etc.
U.S. Pat. No. 2,190,714, to Hoffman, et al., 1940, claims a method of inhibiting mold growth in food products other than margarine and sour dough bread by adding a C.sub.3 -C.sub.12 carboxylic acid thereto.
U.S. Pat. No. 3,404,987, to Kooistra and Troller, 1968, discloses and claims an antimicrobial composition containing 110 parts by weight of an edible mineral salt (iron, manganese, zinc, tin, or silver) and 1-150 parts by weight of an edible acid preservative substance, specifically including propionic acid. The metal salts are taught to impart enhanced and sustained antimicrobial/antifungal activity to the acid preservative substance.
U.S. Pat. No. 1,772,975, Wieland, 1930, teaches the use of solutions of lactic acid, acetic acid, or homologues thereof, as antiseptics at properly adjusted pH's .
U.S. Pat. No. 3,466,663, Russ, et al., 1949, describes the use of caprylic (octanoic) acid to combat mycotic infections of growths. This acid may be used topically as a liquid, ointment or butter for the treatment of surface infectants. It is also taught to be useful for combatting internal infections by injecting intravenously.
The Merck Index, 7th Ed., page 1117, teaches that zinc propionate is used as a fungicide on adhesive tape to reduce plastic irritation caused by molds, fungi and bacterial action.
German Patent No. 2,720,776, issued Nov. 23, 1978 to Akiyama, describes a urinary catheter for long-term use which is made of an elastomer or polymer and which gives off bactericidal metal ions.
U.S. Pat. No. 3,434,869, issued Mar. 25, 1969 to J. B. Davidson, describes a urinary catheter of organic rubber with a surface coating of elastomeric silicone containing a silica filler.
U.S. Pat. No. 3,598,127, issued Aug. 10, 1971 to J. G. Wepsic, describes a catheter having an inner tube of non-permeable rubber formed with V-shaped grooves extending along its length on the outside, carrying antibacterial agents permeable through polysiloxane rubber that surrounds the V-shaped grooves. The antibacterials mentioned in this patent include neomycin, bacitracin, sulfa, mandelamine, zephiran, hexachlorophene, and furadantoin.
Numerous patents cover catheters and similar articles of various designs and materials. Examples include the following.
U.S. Pat. No. 3,699,956, to S. Kitrilakis, et al., Oct. 24, 1972, discloses a percutaneous lead device including an element for preventing bacterial infection caused by implanting the lead through the skin.
U.S. Pat. No. 3,695,921, issued Oct. 3, 1972, to T. H. Shepherd, et al., describes a catheter provided with a coating of a hydrophilic acrylate or methacrylate polymer. Infection from the catheter is said to be further reduced by absorbing an antibiotic such as penicillin, bacitracin, and others, or an antibacterial such as hexachlorophene, or a quaternary ammonium compound, in the coating. See also U.S. Pat. No. 3,566,874, issued Mar. 2, 1971.
U.S. Pat. No. 3,663,965, issued May 23, 1972, to H. L. Lee, et al., describes a bacteria-resistant percutaneous conduit device.
U.S. Pat. No. 3,524,447, issued Aug. 18, 1970, to R. P. Evans, et al., discloses a method of making a rigid tipped polyvinyl catheter.
U.S. Pat. No. 3,598,126, issued Aug. 10, 1971, to J. Hoeltzenbein, describes a vascular cannula for medical applications.
U.S. Pat. No. 3,708,324, issued Jan. 2, 1973, to L. F. Stebleton, discloses a method of growing silicone elastomers useful in the manufacture of catheters.
U.S. Pat. No. 3,926,705, issued Dec. 16, 1975, to D. A. Todd, discloses a "Silicone Catheter and Process for Manufacturing Same." See also U.S. Pat. No. 3,983,879.
U.S. Pat. No. 3,886,947, issued June 3, 1975, to P. N. Sawyer, describes a non-thrombogenic catheter.
Belgian Patent No. 857,264, issued Jan. 30, 1978, to R. L. Stone, describes intravenous solutions comprising aqueous solutions of C.sub.4 -C.sub.9 n-fatty acid antimicrobials. It is the equivalent of copending U.S. application Ser. No. 816,625, filed July 18, 1977, which is a continuation-in-part of application Ser. No. 709,342, filed July 28, 1976, now abandoned.
Copending application Ser. No. 918,532, R. L. Stone, filed June 23, 1978, also discloses solutions containing C.sub.4 -C.sub.9 fatty acid antimicrobials.
As can be seen from the foregoing, various means for providing antimicrobial catheters have been employed heretofore. The present invention employs safe, highly effective carboxylate antimicrobial agents in various known, medical grade polymers to achieve the results sought by prior workers in the field more safely, simply and economically than previously believed possible. In addition, the antimicrobial polymers of the present invention can be used to manufacture all types of medical devices, and are not limited in their utility to special catheter configurations.
Prior art catheters have also often had the problem of too-rapid release of antimicrobial agent under typical usage conditions. The present invention provides antimicrobial polymer compositions from which release of the antimicrobial can be controlled to provide sustained antimicrobial activity over long periods of use.